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Biomedical subjects

H Koelbl

Publications and source records attributed to H Koelbl.

At least 37 records · Page 2Linked to original sources

Tenascin-A marker for the malignant potential of preinvasive breast cancers.

OBJECTIVE: Up to now, the mechanisms responsible for progression from noninvasive to invasive breast cancer have remained obscure. Tenascin is an extracellular matrix glycoprotein, present in embryonal and fetal tissues, which is also found in the stroma of various benign and malignant pathologies. We studied the expression and immunohistochemical behavior of tenascin in specimens of invasive and preinvasive breast cancer in order to assess its potential role as a marker for tumor invasion. MATERIALS AND METHODS: Sixty-eight specimens including 29 noninvasive ductal cancers, 12 invasive ductal cancers, 5 adenoses, 7 fibroadenomas, and 15 samples of normal human breast tissue were evaluated. An immunofluorescent microscopic technique was used for analysis of the localization and distribution of tenascin. Paraffin-embedded biopsies were incubated with primary monoclonal anti-tenascin antibodies (1:25, Dako-tenascin, TN2). Subsequently, trimethylrhodamine-isothiocyanate-conjugated secondary antibodies (rabbit anti-mouse immunglobulins (Dakopatts, Denmark) were added to visualize the protein. RESULTS: A significant tenascin expression was observed around the ducts in all samples of patients with preinvasive breast cancers. Intensive staining was also found in the periductal stroma of all specimens of patients with invasive breast cancers. Benign breast lesions showed weaker reactivity. No tenascin expression was detectable in normal human breasts, while tissue samples of in situ cancers presented variable staining intensities positively correlating with the degree of differentiation. CONCLUSION: Tenascin immunofluorescence may prove a suitable and helpful adjunct for diagnosing malignant disease and for predicting the invasive potential of premalignant breast lesions.

Aged↗

Significance of endovaginal ultrasonography in assessing tamoxifen-associated changes of the endometrium. A prospective study.

BACKGROUND: A prospective study was conducted investigating the value of endovaginal ultrasound in the assessment of tamoxifen-associated changes of the endometrium in patients with breast cancer. METHODS: Seventy postmenopausal patients with breast cancer treated with anti-estrogens for at least 6 months were entered. Those with bleeding disorders and/or an endometrial thickness of > or =10 mm found on ultrasonography underwent hysteroscopy and dilatation and curettage (D&C) for further histological evaluation. In 22 patients, positive ultrasound findings could be compared with histopathology. RESULTS: 82% of the 22 patients with positive sonographic findings had a glandular-cystic hyperplasia or a glandular-cystic polyp. No adenomatous hyperplasia or endometrial cancer was observed in our series. CONCLUSION: Vaginal ultrasound represents a useful diagnostic tool to detect tamoxifen-associated changes of the endometrium. A threshold of 10 mm endometrial thickness appears suitable to identify endometrial abnormalities while reducing the rate of false-positive findings to an acceptable level. However, the role of vaginal ultrasound in screening for endometrial cancer or premalignant lesions remains uncertain.

Aged↗

Tissue polypeptide specific antigen in the follow-up of ovarian and cervical cancer patients.

This retrospective study includes 425 serological examinations of 40 patients with epithelial ovarian cancer and 356 serological examinations of 33 patients with squamous cell cervical cancer. The serum levels of the tumor markers tissue polypeptide specific antigen (TPS), carbohydrate antigen 125 (CA 125) and squamous cell carcinoma antigen (SCC) were determined. Cutoff values of 93 U/l for TPS, 3 microg/l for SCC and 37 U/ml for CA 125 were selected according to the 95th percentile of serum concentrations measured in healthy control patients. For ovarian cancer sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TPS were 67%, 84%, 59% and 90%, respectively. In 27 patients with recurrent ovarian cancer, CA 125 and TPS showed lead time effects in 8 and 11 cases, respectively. The combination of CA 125 and TPS provided lead time in 14 cases of recurrent disease with a time range from I to 23 months (median 3.9 months). In cervical cancer, TPS showed a sensitivity, specificity, PPV and NPV of 64%, 90%, 85% and 68%, respectively. In 16 patients with recurrent cervical cancer, SCC and TPS showed lead time effects in 7 and 8 cases, respectively. The combination of SCC and TPS provided lead time effects in 12 cases with a time range from 0.5 to 6 months (median 3.5 months). Our data indicate that TPS is a valuable tool in the follow-up of patients with ovarian or cervical cancer. However, TPS does not appear to be adequate to replace tumor markers CA 125 and SCC.

Antigens, Neoplasm↗

Transurethral injection of silicone microimplants for intrinsic urethral sphincter deficiency.

OBJECTIVE: To assess the short-term efficacy of transurethral injection of silicone microimplants in women with intrinsic sphincter deficiency. METHODS: During January 1995 and December 1996, 32 women (mean age 64.3 years, range 39-85 years) with type III stress incontinence (intrinsic sphincter deficiency) underwent transurethral injection of silicone microimplants under general anesthesia. Twenty-eight had undergone previous continence surgery. Subjective and urodynamic assessments were made at 6 and 12 months after injection to evaluate success and short-term effects. RESULTS: Objective and subjective success rates were 75% and 59% at 6 and 12 months, respectively. Injections of silicone microimplants significantly increased maximum urethral closure pressure (maximum urethral pressure at rest: 34.40+/-16.46 cm H2O, 95% confidence interval [CI] 28.55, 40.25 versus 25.35+/-10.78 cm H2O, 95% CI 21.52, 29.18; P = .027). There were no complications after surgery up to 1 year. CONCLUSION: Transurethral silicone injections were effective in 60% of cases of intrinsic sphincter deficiency, although there was a time-dependent decrease.

Adult↗

Value of urethral pressure profilometry in the female incontinent patient: a prospective trial with an 8-channel urethral catheter.

OBJECTIVES: To measure the pressure profiles at different positions of the urethral circumference simultaneously. METHODS: Twenty-two women with symptoms of genuine stress incontinence underwent urogynecologic assessment and multichannel urethral pressure profilometry (UPP) at rest with a specially designed 8-channel urethral catheter with radial openings. RESULTS: The distribution pattern of maximum urethral closure pressure (MUCP) and functional urethral length (FUL) values were significantly different (P=0.004 and P=0.0004, respectively). Most of the highest MUCP values per patient were found between channels 2 and 4 (P=0.015); most of the greatest FUL values per patient were found between channels 3 and 4 (P=0.15). CONCLUSIONS: The data of our study substantiate asymmetric radial pressure distribution within the urethra and underline the necessity of cautious interpretation of results of conventional single-channel UPP, which might vary because of transducer orientation.

Female↗

Serum interleukin 1 in ovarian cancer patients.

Interleukin-1 (IL-1) is a multifunctional cytokine playing a central role in the immune response and displaying direct cytotoxic activity in vitro. Serum IL-1 alpha and beta levels were measured by enzyme linked immunosorbent assay (ELISA) in 75 ovarian cancer patients, 30 patients with benign ovarian cysts and 50 healthy controls. Both serum IL-1 alpha and IL-1 beta levels were more often elevated in ovarian cancer patients compared with healthy controls (chi-square test, P < 0.001 and P < 0.001, respectively). Mean serum IL-1 alpha and beta levels decreased significantly after surgical intervention (paired t-test, P = 0.0001 and P = 0.0002, respectively). No correlation with histopathological parameters and overall and disease-free survival was found. These preliminary results indicate that serum levels of IL-1 alpha and beta represent a host defence reaction rather than an autonomous tumour cell production.

Adult↗

Effect of spinal anaesthesia on the lower urinary tract in continent women.

OBJECTIVE: To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. DESIGN: Controlled clinical trial. SETTING: Department of Gynaecology and Obstetrics, Vienna University Medical School. PARTICIPANTS: Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. MAIN OUTCOME MEASURES: Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. RESULTS: Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). CONCLUSIONS: Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Adult↗

Serum M3/M21 in cervical cancer patients.

Cytokeratins are polypeptides which constitute a subclass of intermediate filaments in epithelial cells. The serum tumour marker M3/M21 is based on monoclonal antibodies against the epitopes M3 and M21 of cytokeratin 18. In the present study, we measured M3/M21 serum levels in 50 patients with FIGO stage IB-IIB cervical cancer and in 50 control subjects using a two-site radiometric immunoassay directed against soluble fragments of cytokeratin 18. Median serum levels of M3/M21 in patients with cervical cancer and in normal controls were 70.6 U/ml (range 0-397.7) and 6.5 U/ml (range 0-205.2), respectively (Mann-Whitney U-test, P = 0.0001). Median serum levels of M3/M21 prior to therapy and 4 weeks after therapy were 104.2 U/ml (range 24.6-397.7) and 39.3 U/ml (range 0-234.7), respectively (Mann-Whitney U-test, P = 0.004). We found a significant correlation between elevated M3/M21 serum levels and metastatic disease in pelvic lymph nodes (Mann-Whitney U-test, P = 0.002). 24 patients relapsed after complete remission. In these patients, elevated M3/M21 serum levels before the detection of relapse by computed tomography was observed in 13 cases. Considering these preliminary results, further studies with an increased number of patients are justified to clarify the prognostic value and the monitoring abilities of M3/M21 in cervical cancer patients.

Antibodies, Monoclonal↗

Preoperative evaluation of tumor extension in patients with recurrent cervical cancer.

BACKGROUND: Pelvic exenteration is an option in the treatment of locally recurrent cervical cancer. Various preoperative diagnostic procedures in the estimation of tumor invasion of the bladder and rectum or lymphonodal involvement were evaluated. DESIGN: The sensitivity and specificity of cystoscopy, intravenous pyelography, irrigoscopy, rectoscopy, and computed tomography were evaluated by comparing the preoperative findings with the histological result as the 'golden standards'. RESULTS: In the assessment of bladder invasion the sensitivity of cystoscopy, intravenous pyelography and computed tomography was 22.2%, 55.6% and 55.6%, respectively. The overall sensitivity of the three diagnostic procedures was 77.8%. In the assessment of invasion of the rectum irrigoscopy, rectoscopy and CT revealed a sensitivity of 33.3%, respectively. Only 50% of all cases with tumor infiltration of the rectum showed positive results when all three diagnostic procedures were combined. The sensitivity and specificity of computed tomography in the diagnosis of lymphonodal involvement were 75% and 83.3%, respectively. CONCLUSION: We think that there is an obvious necessity for all diagnostic procedures for patient selection prior to pelvic exenteration. However, all these investigations are not conclusive but complement each other. Prior to pelvic exenteration, critical interpretation of all preoperative diagnostic procedures is mandatory, otherwise surgery results in an unintended palliative procedure.

Adult↗

Prognostic value of immunohistochemically detected CD44 expression in patients with carcinoma of the vulva.

BACKGROUND: Overexpression of alternatively spliced CD44 isoforms has been reported to correlate with poor prognosis in several human malignancies. To the authors' knowledge, there are no studies concerning the prognostic value of CD44 isoform overexpression in patients with squamous cell carcinoma of the vulva. METHODS: Thirty cases of squamous cell carcinoma of the vulva with International Federation of Gynecology and Obstetrics Stage I to III were examined immunohistochemically for overexpression of CD44 isoforms. We used 3 different variant exon sequence-specific murine monoclonal antibodies to CD44 isoforms containing variant exons v5, v6, and v7 to -8, respectively. The correlation of CD44 overexpression with clinical stage, histologic grade, and disease free and overall survival was investigated. RESULTS: CD44 isoforms CD44v5, CD44v6, and CD44v7-8 were detected in 83% (25/30), 63% (19/30), and 27% (8/30) of the tumor samples, respectively. Patients with tumors overexpressing CD44v6 showed a significantly shorter relapse free (log rank test, P = 0.002) and overall survival (log rank test, P = 0.003) compared with patients with tumors lacking CD44v6 overexpression. Expression of CD44v5 and CD44v7 to 8 had no impact on patients' survival. Clinical stage and histologic grade did not correlate with CD44 overexpression. CONCLUSIONS: Immunohistochemically detected overexpression of CD44 isoforms containing variant exon v6 is correlated with a poor relapse free and overall survival in patients with carcinoma of the vulva.

Adult↗

Immunohistochemical detection of adhesion molecule CD44 splice variants in lymph node metastases of cervical cancer.

Expression of specific cell adhesion molecule CD44 isoforms (splice variants) has been shown to be associated with poor prognosis in human cervical cancer. We used 3 different variant exon sequence-specific murine monoclonal antibodies (MAbs) to epitopes encoded by exons v5, v6 and v7-v8 of human variant CD44 to study the expression of CD44 splice variants in 35 primary squamous-cell carcinomas of the cervix and pelvic lymph node metastases by means of immunohistochemistry. Primary tumors showed expression of CD44 splice variants CD44v5, CD44v6 and CD44v7-8 in 93%, 73% and 33% of cases, respectively. Lymph node metastases expressed CD44v5, CD44v6 and CD44v7-8 in 83%, 53% and 21% of cases, respectively. Tumors with expression of CD44v6 in pelvic lymph node metastases showed metastatic spread to 2 or more pelvic lymph nodes significantly more often compared to patients without expression of splice variant CD44v6. Patients suffering from tumors with lymph node metastases expressing splice variant CD44v6 had a poorer recurrence-free survival compared to patients without CD44v6 expression in lymph node metastases, but this trend was not statistically significant. Expression of CD44 splice variants containing epitopes encoded by exon v6 in primary tumors and pelvic lymph node metastases of cervical cancer patients is consistent with a prominent role of CD44 in the process of metastasis formation.

Adult↗

Prognostic value of immunohistochemically detected HER-2/neu oncoprotein in endometrial cancer.

HER-2/neu (c-erbB-2) oncoprotein is a transmembrane glycoprotein and may function as a growth factor receptor being involved in the regulation of cell growth and cell transformation. We performed an analysis of 100 patients with endometrial cancer stage FIGO I to IV using an immunoperoxidase technique on formalin-fixed, paraffin-embedded tissue samples in order to determine HER-2/neu oncoprotein expression. HER-2/neu oncoprotein was expressed in the tumors of 21 patients (21%). Clinical stage, histologic stage, histologic grade and death of invasion did not correlate with HER-2/neu oncoprotein expression. We found HER-2/neu oncoprotein in all clinical stages and therefore it does not seem to be a late event in the natural history of endometrial cancer. HER-2/neu oncoprotein expression was associated with poor overall survival (log-rank P-value 0.04).

Adult↗

Quantification of uPA receptor expression in human breast cancer cell lines by cRT-PCR.

The conversion of plasminogen to active plasmin is thought to be a crucial step in the process of extracellular matrix degradation associated with metastatic spread. Activation of plasminogen is initiated by urokinase plasminogen activator (uPA). The binding of uPA to the uPA cell surface receptor (uPA-R) accelerates plasmin generation from plasminogen and localizes uPA activity to the cell surface. We investigated the mRNA-expression of uPA-R in 19 different human breast cancer cell lines. In a competitive reverse transcription polymerase chain reaction (cRT-PCR) we simultaneously co-amplified two different RNA templates bearing the same primer recognition sequences, the cell line RNA and a known amount of an in vitro synthesized uPA-R-RNA internal standard. We analyzed the two PCR products differing 50 bp in size by agarose gel electrophoresis and calculated the initial uPA-R-RNA template concentration from the relative intensities of the bands quantified by video densitometry. We grouped the investigated cell lines according to their in vitro invasiveness according to literature. Cell lines with a high potential of invasiveness showed a higher expression of uPA-R compared to those with a low potential of invasiveness (Student's t-test, p 0.04). In addition to that we compared the uPA-R mRNA levels with uPA-R, uPA, and PAI-1 protein levels in culture supernatants and cell lysates. The obtained results in breast cancer cell lines with different invasiveness and in benign epithelial cell lines revealed the complex cooperation of the urokinase type proteolytic pathway. uPA, uPA-R, and PAI-1 are to be considered as a diagnostic tool rather than assaying a particular molecule alone. Our findings support the hypothesis that the urokinase proteolytic pathway plays a central role in the acquisition of an invasive phenotype and favors its potential use as a prognostic marker in patients with breast cancer.

Binding, Competitive↗

Quantitative immunohistochemistry of factor VIII-related antigen in breast carcinoma: a comparison of computer-assisted image analysis with established counting methods.

Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is reported to be an independent prognostic factor. The established method of enumeration of microvessel density is to count the vessels using an ocular raster (counted microvessel density [CMVD]). The vessels were detected by staining endothelial cells using Factor VIII-related antigen. The aim of the study was to compare the CMVD results with the percentage of factor VIII-related antigen-stained area using computer-assisted image analysis. A true color red-green-blue (RGB) image analyzer based on a morphologically reduced instruction set computer processor was used to evaluate the area of stained endothelial cells. Sixty invasive breast carcinomas were included in the analysis. There was no significant correlation between the CMVD and the percentage of factor VIII-related antigen-stained area (Spearman correlation coefficient = 0.24, confidence interval = 0.02-0.46). Although high CMVD was significantly correlated with poorer recurrence free survival (P = .024), percentage of factor VIII-related antigen-stained area showed no prognostic value. Counted microvessel density and percentage of factor VIII-related antigen-stained area showed a highly significant correlation with vessel invasion (P = .0001 and P = .02, respectively). There was no correlation between CMVD and percentage of factor VIII-related antigen-stained area with other prognostic factors. In contrast to the CMVD within malignant tissue, the percentage of factor VIII-related antigen-stained area is not suitable as an indicator of prognosis in breast cancer patients.

Breast Neoplasms↗